Omaveloxolone for Friedreich's Ataxia

Not currently recruiting at 10 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Biogen

Must not be taking: Cytochrome P450, P-glycoprotein

Disqualifiers: Diabetes, Heart disease, Infections, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores omaveloxolone, a potential new treatment for Friedreich's Ataxia, a condition affecting coordination, movement, and daily living. The study aims to assess the treatment's safety and its ability to improve physical effort and coordination over 12 to 48 weeks. Participants will receive varying doses of omaveloxolone or a placebo (a pill with no active ingredients) to determine the optimal dose. Individuals with genetically confirmed Friedreich's Ataxia who can maintain their current exercise routine and complete exercise tests may be suitable for this trial. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot take certain drugs that affect liver enzymes or are processed by specific pathways in the body within 7 days before starting the study. It's best to discuss your current medications with the study team to see if any need to be stopped.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that omaveloxolone is generally safe for patients. In a study with 103 participants, researchers compared 150 mg of omaveloxolone to a placebo. This study included both adults and teenagers aged 16 and older. Most participants tolerated the treatment well, and its safety profile was similar to the placebo.

Some side effects occurred, but they were usually mild, such as headaches and nausea. These side effects were not severe enough to cause most participants to stop the treatment. Since omaveloxolone is in a Phase 2 study, it has already passed initial safety tests in earlier trials, but more research is needed to confirm its long-term safety.

Researchers are also testing omaveloxolone for its potential to protect cells from damage, which could aid in treating various diseases. While it is still under study for Friedreich's ataxia, its safety profile so far appears promising. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Friedreich's Ataxia?

Omaveloxolone is unique because it targets oxidative stress and mitochondrial dysfunction, which are central features in Friedreich's Ataxia. Unlike current treatments that mainly focus on symptom management, omaveloxolone activates the Nrf2 pathway to enhance cellular defense mechanisms and improve mitochondrial function. Researchers are excited about this approach because it directly addresses the underlying cause of the disease, potentially slowing its progression rather than just alleviating symptoms.

What evidence suggests that omaveloxolone might be an effective treatment for Friedreich's Ataxia?

Research has shown that omaveloxolone might help treat Friedreich's ataxia. In studies, patients taking omaveloxolone improved their movement, coordination, and balance by 55%, as measured by mFARS scores. These patients also performed better in exercise tests, with lower heart rates and blood lactate levels, indicating increased physical exertion capacity. Omaveloxolone is the first FDA-approved treatment for Friedreich's ataxia, underscoring its proven effectiveness. Participants in this trial will receive varying dosages of omaveloxolone or a placebo to further evaluate its efficacy and safety. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for people aged 16-40 with genetically confirmed Friedreich's ataxia, who can swallow capsules and have a specific level of disease severity (modified FARS score between 20 and 80). Participants should be stable in their exercise routine and able to complete maximal exercise testing. They cannot join if they've used certain drugs recently, have significant heart disease or abnormal blood tests, uncontrolled diabetes, cognitive impairments, active infections, or substance abuse issues.

Inclusion Criteria

My condition is genetically confirmed Friedreich's ataxia.

I am between 16 and 40 years old.

Have no changes to exercise regimen within 30 days prior to Study Day 1 and be willing to remain on the same exercise regimen during the 16-week study period

Exclusion Criteria

I have not taken and will not take certain drugs that affect liver enzymes or drug transporters during the study.

My diabetes is not under control (HbA1c >11.0%).

Have participated in any other interventional clinical study within 30 days prior to Study Day 1

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Randomized, placebo-controlled, double-blind, dose-escalation study to evaluate the safety of omaveloxolone (RTA 408) at various doses

12 weeks

Treatment Part 2

Randomized, placebo-controlled, double-blind, parallel-group study to evaluate the safety and efficacy of omaveloxolone (RTA 408) 150 mg

48 weeks

Extension

Long-term safety and tolerability of omaveloxolone (RTA 408) in qualified participants, open-label

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Omaveloxolone

Trial Overview The study examines omaveloxolone (RTA 408) capsules at various doses for treating Friedreich's ataxia. It has two parts: the first part tests safety across different doses; the second part assesses safety and effectiveness of a set dose (150 mg). An extension phase will look into long-term use. The drug aims to activate Nrf2 signaling impaired in this condition.

How Is the Trial Designed?

Group I: Part 2 Omaveloxolone Capsules 150 mg Experimental Treatment 1 Intervention

Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks

Group II: Part 1 Omaveloxolone Capsules 80 mg Experimental Treatment 1 Intervention

Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks

Group III: Part 1 Omaveloxolone Capsules 40 mg Experimental Treatment 1 Intervention

Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks

Group IV: Part 1 Omaveloxolone Capsules 300 mg Experimental Treatment 1 Intervention

Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks

Group V: Part 1 Omaveloxolone Capsules 20 mg Experimental Treatment 1 Intervention

Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks

Group VI: Part 1 Omaveloxolone Capsules 2.5 and 5 mg Experimental Treatment 2 Interventions

omaveloxolone (RTA 408) Capsules, 2.5 mg administered orally one daily for 2 weeks, then 5 mg taken orally once daily for 10 weeks

Group VII: Part 1 Omaveloxolone Capsules 160 mg Experimental Treatment 1 Intervention

Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks

Group VIII: Part 1 Omaveloxolone Capsules 10 mg Experimental Treatment 1 Intervention

omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks

Group IX: Part 1 Placebo Capsules Placebo Group 1 Intervention

Placebo capsules administered orally once daily for 12 weeks

Group X: Part 2 Placebo Capsules Placebo Group 1 Intervention

Placebo capsules administered orally once daily for 48 weeks

Omaveloxolone is already approved in United States, European Union for the following indications:

Approved in United States as Skyclarys for:

• Friedreich's ataxia

Approved in European Union as Skyclarys for:

• Friedreich's ataxia

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Reata, a wholly owned subsidiary of Biogen

Lead Sponsor

Trials

52

Recruited

7,400+

Reata Pharmaceuticals, Inc.

Lead Sponsor

Trials

52

Recruited

6,900+

Friedreich's Ataxia Research Alliance

Collaborator

Trials

20

Recruited

6,400+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

In a Phase 2 study involving 69 patients with Friedreich ataxia, omaveloxolone was found to be well tolerated with mostly mild adverse effects, indicating a favorable safety profile.

At a dose of 160 mg/day, omaveloxolone significantly improved neurological function as measured by the modified Friedreich Ataxia Rating Scale (mFARS), particularly in patients without musculoskeletal foot deformity, suggesting its potential efficacy in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia. Lynch, DR., Farmer, J., Hauser, L., et al.[2022]

Omaveloxolone (SKYCLARYS™) is an orally active drug that enhances antioxidant activity by activating the Nrf2 pathway, which is crucial for combating oxidative stress and mitochondrial dysfunction in patients with Friedreich's ataxia.

Approved in February 2023, omaveloxolone represents a significant advancement in treating Friedreich's ataxia, particularly for adults and adolescents aged 16 and older, by targeting the underlying cellular damage associated with the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omaveloxolone: First Approval. Lee, A.[2023]

Omaveloxolone, a synthetic compound that activates the Nrf2 pathway, showed a dose-linear pharmacokinetic profile in monkeys, indicating predictable absorption and distribution in key tissues like the liver, lung, and brain after oral administration.

In Friedreich's ataxia patients, doses of omaveloxolone starting at 80 mg led to significant improvements in neurological function, with plasma levels correlating with those that effectively activated Nrf2 in monkeys, suggesting its potential efficacy in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of the novel Nrf2 activator omaveloxolone in primates. Reisman, SA., Gahir, SS., Lee, CI., et al.[2022]

In a phase 2 trial involving 103 patients with Friedreich ataxia, omaveloxolone significantly improved neurological function compared to placebo, with a notable difference in modified Friedreich's Ataxia Rating Scale scores after 48 weeks.

Omaveloxolone was generally safe and well tolerated, although some patients experienced transient increases in liver enzymes and common side effects like headache, nausea, and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Lynch, DR., Chin, MP., Delatycki, MB., et al.[2023]

Friedreich ataxia (FRDA) is a neurodegenerative disorder with no approved therapies, but increasing Nrf2 activity may help slow disease progression.

Recent clinical trials suggest that omaveloxolone, which enhances Nrf2 activity, could be a promising novel treatment for FRDA, although it is not yet approved for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omaveloxolone: potential new agent for Friedreich ataxia. Lynch, DR., Johnson, J.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02255435

NCT02255435 | A Study to Learn About the Effects and ... This 2-part study will evaluate the efficacy, safety, and pharmacodynamics of omaveloxolone (RTA 408) in the treatment of participants with Friedreich's ataxia.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11684145/

Safety and efficacy of omaveloxolone v/s placebo for the ... Overall, in a research analysis performed by the same group of researchers on the MOXIe study demonstrated a reduction of mFARS by 55% in the ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/216718Orig1s000MedR.pdf

216718Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov The evidence of effectiveness of omaveloxolone in the treatment of Friedreich's ataxia was based on a single Study 408-C-1402 Part 2 (MoXIe) ...

4. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Omaveloxolone-Cognitive-Vitality-For-Researchers.pdf

Omaveloxolone (RTA-408) However, in submaximal exercise testing, treated patients demonstrated a significant lowering of heart rate (p=0.01) and blood lactate (p=0.04), which are ...

5. cell.com cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(23)00065-2

Omaveloxolone (SkyclarysTM) for patients with ... Omaveloxolone is the first and only FDA-approved drug for patients with Friedreich's ataxia. Omaveloxolone has received Orphan Drug, Fast Track, ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/216718Orig1s000SumR.pdf

216718Orig1s000 SUMMARY REVIEW - accessdata.fda.gov A total of 103 patients provided safety data of 150 mg omaveloxolone compared to placebo. This included 24 adolescent patients age ≥ 16 ...

7. ema.europa.eu ema.europa.eu/en/documents/product-information/skyclarys-epar-product-information_en.pdf

Skyclarys, INN-omaveloxolone - EMA Omaveloxolone should be initiated and supervised by physicians with experience in the treatment of patients with Friedreich Ataxia. Posology.